经江苏省药品监督检验研究院等12家药品检验机构检验，共17家企业生产的28批次药品不符合规定。现将相关情况通告如下：　　一、经江苏省药品监督检验研究院检验，标示为澳美制药厂生产的5批次夫西地酸乳膏不符合规定，不符合规定项目为粒度。　　二、经吉林省药品检验研究院检验，标示为万特制药（海南）有限公司生产的2批次氯雷他定糖浆不符合规定，不符合规定项目为有关物质。　　三、经天津市药品检验研究院检验，标示为上海海虹实业（集团）巢湖今辰药业有限公司生产的1批次磷酸钠盐口服溶液不符合规定，不符合规定项目为相对密度。　　四、经黑龙江省药品检验研究院检验，标示为陕西西岳制药有限公司生产的2批次托西酸舒他西林胶囊不符合规定，不符合规定项目为溶出度。　　五、经无锡市药品安全检验检测中心检验，标示为浙江金华康恩贝生物制药有限公司生产的1批次乙酰半胱氨酸泡腾片不符合规定，不符合规定项目为性状。　　六、经西藏自治区食品药品检验研究院检验，标示为西藏神猴药业有限责任公司生产的2批次二十五味珊瑚丸不符合规定，不符合规定项目为重量差异。　　七、经黑龙江省药品检验研究院检验，标示为湖北民康制药有限公司生产的2批次七厘散不符合规定，不符合规定项目为含量测定。　　八、经四川省药品检验研究院检验，标示为湖北瑞华制药有限责任公司生产的4批次清气化痰丸不符合规定，不符合规定项目为装量差异。　　九、经安徽省食品药品检验研究院检验，标示为四川金可药业有限责任公司、四川益祥康药业有限公司生产的2批次赤芍不符合规定，不符合规定项目为性状。　　十、经湖南省药品检验检测研究院检验，标示为安国市安兴中药饮片有限公司、河北康盛华药业有限公司、河北悦康志德药业有限公司生产的3批次红参（红参片）不符合规定，不符合规定项目为鉴别；标示为辽宁龙参健康药业有限公司生产的1批次红参（红参片）不符合规定，不符合规定项目为其他有机氯类农药残留量、总还原糖。　　十一、经浙江省食品药品检验研究院检验，标示为江苏和生堂药业有限公司生产的1批次龙胆不符合规定，不符合规定项目为杂质。　　十二、经深圳市药品检验研究院检验，标示为江西信健药业有限公司生产的1批次野菊花不符合规定，不符合规定项目为含量测定。　　十三、经山西省检验检测中心检验，标示为四川盛世锦荣药业有限公司生产的1批次栀子不符合规定，不符合规定项目为水分。　　对上述不符合规定药品，药品监督管理部门已要求相关企业和单位采取暂停销售使用、召回等风险控制措施，对不符合规定原因开展调查并切实进行整改。国家药监局要求相关省级药品监督管理部门依据《中华人民共和国药品管理法》，组织对上述企业和单位存在的涉嫌违法行为立案调查，并按规定公开查处结果。　　特此通告。　　附件：1.28批次不符合规定药品名单　　　　　2.不符合规定项目小知识　国家药监局2025年8月25日附件2不符合规定项目小知识一、粒度系指颗粒的大小，药品中对有粒度要求的制剂产品如颗粒剂、散剂、混悬型滴眼液、混悬型软膏剂等会进行该项目的设定，不符合规定可能会导致药物主成分含量不均一。二、有关物质系指药品中的有机杂质，是反映药品纯度的指标。三、相对密度系指在相同温度和压力条件下，某物质的密度与水的密度之比。四、溶出度系指活性药物从制剂中溶出的速度和程度，不符合规定可能会影响药物的吸收，降低生物利用度。五、性状项下常记载外观、臭、味、溶解度以及物理常数等，在一定程度上反映药品的质量特性。中药饮片性状项不符合规定，可能涉及药材种属偏差、炮制工艺有瑕疵、储存不当等情形。六、重量差异与装量差异系反映药物均匀性的指标，是保证准确给药的重要参数之一。七、含量测定系指用规定的试验方法测定原料及制剂中有效成分的含量，一般可采用化学、仪器或生物测定方法。八、鉴别项主要用于区分药品特性，其手段包括显微鉴别、光谱鉴别等，薄层色谱法是常用的鉴别方法。九、其他有机氯类农药残留量旨在检查五氯硝基苯等农药的残留量。十、总还原糖检查旨在考察中药材或中药饮片是否存在掺糖的情况。十一、杂质检查可反映中药饮片中掺入或混入杂质的情况。十二、水分系指药品中的含水量。水分偏高或偏低通常与工艺、包装不当以及储运环境等因素有关。

广东省粤东磁电有限公司等11家注册人向广东省药品监督管理局主动提出注销产品注册证的申请。根据《医疗器械监督管理条例》的规定，现对该11家注册人持有的27张《医疗器械注册证》依法予以注销（注销清单见附件）。　　特此通告。　　附件：医疗器械注册证注销清单　　广东省药品监督管理局2025年8月25日　　序号注册人名称注册证编号产品名称1广东省粤东磁电有限公司粤械注准20202142137一次性使用医用口罩2广东省粤东磁电有限公司粤械注准20212141086医用外科口罩3广东省粤东磁电有限公司粤械注准20232141095医用防护口罩4经方精密医疗（深圳）有限公司粤械注准20202061868一次性使用穿刺导向片5深圳市宏富盛科技有限公司粤械注准20212141385一次性使用医用口罩6广州华澳生物科技有限公司粤械注准20212400078血清淀粉样蛋白A测定试剂（免疫荧光层析法）7深圳市胡桃医疗科技有限公司粤械注准20172070736单导心电记录仪8广州华澳生物科技有限公司粤械注准20212400085心肌肌钙蛋白I测定试剂（免疫荧光层析法）9广州华澳生物科技有限公司粤械注准20212400083胃蛋白酶原Ⅱ测定试剂（免疫荧光层析法）10广州华澳生物科技有限公司粤械注准20212400081胃蛋白酶原I测定试剂（免疫荧光层析法）11广州华澳生物科技有限公司粤械注准20212400084铁蛋白测定试剂（免疫荧光层析法）12广州华澳生物科技有限公司粤械注准20212400082髓过氧化物酶测定试剂（免疫荧光层析法）13广州华澳生物科技有限公司粤械注准20212400080降钙素原测定试剂（免疫荧光层析法）14广州华澳生物科技有限公司粤械注准20212400086肌酸激酶同工酶（CK—MB）测定试剂（免疫荧光层析法）15广东雅丽洁精细化工有限公司粤械注准20202141667一次性使用医用口罩16广州华澳生物科技有限公司粤械注准20212400079肌红蛋白测定试剂（免疫荧光层析法）17广州华澳生物科技有限公司粤械注准20212400143C—反应蛋白测定试剂（免疫荧光层析法）18广州华澳生物科技有限公司粤械注准20212400077白介素6（IL—6）测定试剂（免疫荧光层析法）19遂溪县百事佳电器有限公司粤械注准20202071517非接触式红外测温仪20深圳康佑林医疗器械有限公司粤械注准20222140821肠内营养泵21海丰民旺纺织品有限公司粤械注准20232140291医用外科口罩22海丰民旺纺织品有限公司粤械注准20212140368一次性使用医用口罩23海丰民旺纺织品有限公司粤械注准20232140290医用防护口罩24广东纳妮儿服饰实业有限公司粤械注准20202141719一次性使用医用口罩25广州雷诺生物科技有限公司粤械注准20202140663医用外科口罩26广州雷诺生物科技有限公司粤械注准20202141605一次性使用医用口罩27广州雷诺生物科技有限公司粤械注准20202141297医用防护口罩

按照《医疗器械监督管理条例》《医疗器械生产监督管理办法》有关规定，根据企业申请，广东省药品监督管理局依法注销广东不二医疗科技有限公司等20家企业的《医疗器械生产许可证》。　　特此通告。　　附件：企业信息广东省药品监督管理局2025年8月25日　　序号企业名称许可证编号生产地址1广东不二医疗科技有限公司粤食药监械生产许20203958号广东省东莞市凤岗镇碧湖路28号2栋301室2迈格生命科技（深圳）有限公司粤食药监械生产许20204232号深圳市南山区西丽中心区文苑街35号西丽新源工业厂房（聚创金谷创意园）4栋（B212）3深圳市思肯三维科技发展有限公司粤食药监械生产许20214505号深圳市宝安区松岗街道东方大道33号旁边东方大田洋工业区第4栋厂房4惠州润众科技股份有限公司粤食药监械生产许20204066号惠州市水口镇龙津村姚屋村小组地段同健（惠阳）电子有限公司厂房5深圳市胡桃医疗科技有限公司粤食药监械生产许20173024号深圳市坪山区坑梓街道办事处秀新社区锦绣中路14号深福保现代光学厂区C栋3016广东雅丽洁精细化工有限公司粤食药监械生产许20204091号汕头市潮南区峡山金光南路东明大厦八层、十层7日隆科技（深圳）有限公司粤药监械生产许20235054号深圳市龙岗区园山街道荷坳社区金源二路6号B栋第3层8珠海脉搏波医疗器械有限公司粤药监械生产许20224937号珠海市高新区唐家湾镇科技创新海岸科技三路2号A栋厂房四楼、五楼9深圳市安捷泰科技有限公司粤食药监械生产许20204063号深圳市龙华区华昌北路457号佳鼎科技园A栋30110深圳康佑林医疗器械有限公司粤药监械生产许20224783号深圳市宝安区西乡街道固兴社区迪福路东山九厂602、60511遂溪县百事佳电器有限公司粤食药监械生产许20204028号广东湛江遂溪县岭北镇国道207线南6号地块之二12谷林电器（深圳）有限公司粤食药监械生产许20214439号深圳市坪山区坑梓街道秀新社区新乔围工业区新发路7号13广东海华拉链有限公司粤食药监械生产许20204011号广东省汕尾市海丰县城东镇金园工业区14中山百川汇盈精密实业有限公司粤食药监械生产许20204000号中山市东区起湾道北136号（第四层）15深圳市一诺牙科技术有限公司粤食药监械生产许20183199号深圳市龙华区观湖街道新田社区新丰工业区11号101-301，12号三楼、40216广东小猪班纳医疗生物科技有限公司粤药监械生产许20234993号广东省东莞市樟木头镇樟洋富达路29号1栋502室17中山市浩宸劳保医疗用品有限公司粤食药监械生产许20214302号中山市南区南源路5号D幢3、4层18深圳必奥思医学仪器有限公司粤药监械生产许20245429号深圳市坪山区坑梓街道金沙社区锦绣东路22号雷柏中城生命科学园第3分园A栋50719广东徕康医疗科技有限公司粤药监械生产许20224742号中山火炬开发区江尾头村“牛肚环”星达·嘉湖工业园2号厂房2楼（B区）20广东谱斯达光子科技有限公司粤药监械生产许20235017号中山市东升镇葵兴大道202号

为充分发挥药品抽检在风险防控方面的技术支撑作用，加强药品经营使用环节质量监管，近日，乌海市海勃湾区市场监管局结合工作实际，扎实有序推进药品抽检工作。乌海市海勃湾区市场监管局按照乌海市市场监管局部署要求，明确责任分工，细化目标任务，对中药饮片、儿童用药、蒙藏药制剂等药品进行了重点抽检，被抽检单位覆盖市区、乡镇范围内的药品连锁、零售企业及医疗机构。乌海市海勃湾区市场监管局注重监检结合，对被抽检单位的索证索票、进货渠道、药品购进验收记录、储存条件和养护环节等多方面开展检查。截至目前，已圆满完成市级药品抽检任务。下一步，乌海市海勃湾区市场监管局将以药品抽检工作为契机，严厉打击药品非法渠道购进等违法行为，密切关注抽检结果，对不合格药品依法查处，保障公众用药安全。

行政相对人名称 南通市潘妍化妆品厂 行政相对人类别 法人及非法人组织 统一社会信用代码 91320623730709548B 工商注册号 组织机构代码 税务登记号 事业单位证书号 社会组织登记证号 法定代表人 潘建国 法定代表人证件类型 法定代表人证件号码 证件类型 证件号码 行政处罚决定书文号 苏药监通处罚〔2025〕1号 违法行为类型 《化妆品监督管理条例》第二十五条第三款的规定 违法事实 生产经营不符合强制性国家标准的化妆品 处罚依据 《化妆品监督管理条例》第六十条第二项的规定 处罚类别 没收违法所得、没收非法财物 处罚内容 1．没收违法所得219168.25元。2．没收“乐赛仙 维生素E乳”（生产批号：20230907）427瓶。 罚款金额（万元） 没收违法所得没收非法财物的金额（万元） 22.098300 暂扣或吊销证照名称及编号 处罚决定日期 2025/08/27 处罚有效期 2025/09/16 公示截止期 2028/08/27 处罚机关 江苏省药品监督管理局 处罚机关统一社会信用代码 11320000014000394R 数据来源单位 江苏省药品监督管理局 数据来源单位统一社会信用代码 11320000014000394R 备注 公示截止期依据文件：市场监督管理行政处罚信息公示规定

近期，我局对浙江大冢制药有限公司开展了省级监督检查（药品GMP符合性检查），综合评定结论为不符合要求。为防控药品质量风险，依据《药品管理法》第九十九条第三款、《药品生产监督管理办法》第五十九条第一款第二项的规定，自2025年8月26日起，决定对浙江大冢制药有限公司采取暂停生产、销售进口药品分包装（冻干粉针剂）、进口药品分包装[小容量注射剂（含抗肿瘤类）]的风险控制措施。特此通告。浙江省药品监督管理局2025年8月26日

Product:Medical DevicesRecipient:Mr. Xiaojun SuTest Facility and General ManagerCCIC Huatongwei International Inspection Co., Ltd.107 Changyang Street, Suzhou Industrial Park Suzhou, Jiangsu District ChinaSuzhou ShiJiangsu Sheng,China(b)(6)@szhtw.com.cnIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERJune 25, 2025Dear Mr. Su:This Warning Letter is to inform you of objectionable conditions observed during the United States Food and Drug Administration (FDA) inspection conducted at CCIC Huatongwei International Inspection (Suzhou) Co., Ltd. from January 6, 2025, to January 14, 2025, by investigators from the FDA’s Office of Bioresearch Monitoring Inspectorate (OBMI) Foreign Inspection Cadre. This inspection was conducted to determine whether activities and procedures related to your participation in Good Laboratory Practice (GLP) nonclinical studies complied with applicable federal regulations. Specifically, FDA investigators focused on the list of studies below including, but not limited to guinea pig maximization, rabbit muscle implantation, acute systemic toxicity, MTT cytotoxicity, rabbit pyrogen, intracutaneous reactivity, and hemolysis studies conducted at your facility.The list of studies below is not an all-inclusive list of studies impacted by the inspection or by the violations cited in this letter:Study numberTest(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Rabbit Muscle Implantation(b)(4)Guinea Pig Maximization Test (GPMT)(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)GPMT(b)(4)Acute Systemic Toxicity (AST)(b)(4)AST(b)(4)AST(b)(4)MTT Cytotoxicity(b)(4)Rabbit Pyrogen TestThese tests are used in nonclinical studies for the development of devices as that term is defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)(1), because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemption, Premarket Approval applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.Our review of the inspection report prepared by the OBMI revealed serious violations of Title 21, Code of Federal Regulations (CFR) Part 58 - Good Laboratory Practice for Nonclinical Laboratory Studies, which concerns, among other things, requirements prescribed under section 520(g) of the Act, 21 U.S.C. § 360j(g). Compliance with Part 58 is intended to assure the quality and integrity of the safety data filed in a premarket submission. At the close of the inspection, the FDA investigators presented the inspectional observations Form FDA-483 for your review and discussed the observations listed on the form with you. We received a response from your firm dated February 4, 2025, concerning our investigators’ observations noted on the Form FDA-483. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. The study director failed to assure that all experimental data, including observations of unanticipated responses of the test system are accurately recorded and verified and that all raw data, documentation, protocols, specimens, and final reports are transferred to the archives during or at the close of the study [21 CFR 58.33(b), and 58.33(f)].The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control. The study director’s responsibilities include ensuring that all experimental data are accurately recorded and verified. Additionally, the study director is responsible for assuring that all raw data, documentation, protocols, specimens, and final reports are transferred to the archives as required by the regulations. Examples of the study director’s failures to adhere to these requirements include, but are not limited to, the following:a. Study records for nine GPMT studies ((b)(4)) conducted by four different study directors throughout(b)(4)to(b)(4)contained six pages of source data that were photocopied and reused across different studies. The copied data included documentation of all animal preparation, administration of test and control articles, observations, and results. Additionally, the technicians’ signatures included within the source data were photocopied and reused across different studies. The experimental data was therefore not accurately recorded and verified.b. In all of the seven significant risk device muscle implantation studies reviewed, for the Weeks 4, 13, and 26 datasets, multiple examples were found where the entries on the animal observation tables and the signature of the person completing them appeared to have been photocopies of the same document with only a change to the week number and the date. These studies all started on(b)(4)and ended on(b)(4). The bolded numbers in the chart below indicate records that are also copied across the data sets within the same study. For example, in(b)(4), the observation data for the weeks bolded in the 13-week study (weeks 2-9) and the observation data for the weeks bolded in the 26-week study (weeks 2-12) are all identical. The experimental data was therefore not accurately recorded and verified. Some examples are as follows:Study ProtocolIntervalWeeks with photocopied animal observation data(b)(4)4 Weeks2-413 Weeks2-9 and 11-1326 Weeks2-12 and 14-26(b)(4)4 Weeks2-413 Weeks2-9 and 11-1326 Weeks2-12 and 14-26(b)(4)4 Weeks2-413 Weeks2-9 and 11-1326 Weeks2-12 and 14-26c. The study director used templates with pre-completed information to generate study final reports that included pre-completed study observations and results. As confirmed by the study director during the inspection, these templates utilized red font and/or brackets to indicate where new information is to be populated within the documents. However, several sections of the template reports which should have been study-specific were pre-completed and not identified in red font and/or brackets as requiring updates (i.e., the template reports did not indicate that the template should be revised to incorporate the study-specific observations and results), including:Muscle Implant Test Report Template: statements regarding animal observations, macroscopic assessments, the microscopic semiquantitative score for the tests, and overall conclusions.Acute Systemic Toxicity Test Report Template: pre- and post-extraction conditions of the test article and control, statements regarding the results of the test article and negative controls and overall conclusions.Guinea Pig Maximization/Skin Sensitization Test Report Template: pre- and post-extraction conditions of the test article and control, skin reaction results and clinical observations for the test article and control, and overall conclusions.The use of templates such as these indicates a failure of the study director to assure that all experimental data, including observations of unintended responses of the test system are accurately recorded and verified. Each test article is nuanced in its combination of materials, construction, intended use, and duration of use. Use of templates that contain pre-completed observations, results, and overall conclusions indicates lack of proper scientific assessment and calls into question whether the experimental data was accurately recorded and verified in the final reports.d. During the inspection it was observed that all study folders on the GLP archivist's portable hard drive had been modified on or about January 5, 2025, shortly prior to the inspection. According to the Quality Assurance Unit Manager and GLP archivist, prior to the pre-announcement of this inspection on December 27, 2024, they had not archived any study protocols or sample submission forms, and so they added them to the archive index ahead of the inspection. The required records were therefore not transferred to the archives during or at the close of each study. In addition, the following deficiencies regarding the archival practices were found:Of the 21 study records initially requested for review, only seven were found in the dedicated GLP archive room.1The tissue slides from Muscle Implantation study(b)(4)were not retained.There were no tissue blocks and cassettes for any studies stored in the GLP archive room.For both Muscle Implantation studies(b)(4)and(b)(4), tissue slide "20" of the 20 tissue slides was missing from the archives.The electronic source data for the rabbit pyrogen tests is not maintained. Only the hand-transcribed data is included in the study records. The rabbit pyrogen test is conducted using a pyrogen meter that provides machine-generated results, which are then transcribed by hand to a paper record.As the principal point of study control, the study director did not assure that all experimental data were accurately recorded and verified, that applicable good laboratory practice regulations were followed and that all raw data, documentation, protocols, specimens, and final reports were transferred to the archives during or at the close of the study. Failure to ensure accurate data such as individual animal weights, animal preparation, the administration of test and control articles, observations, and results, yields questionable study results and conclusions. Furthermore, failure to ensure all data is retained and timely transferred to the archives can result in incomplete documentation of the study in the archives and could limit reconstruction and evaluation of the study. Based on these failures, FDA has concerns about the quality and integrity of the data generated from the nonclinical laboratory studies conducted at your testing facility. Complete and accurate study data are necessary to allow FDA to fully assess the overall safety and risk of a device with an associated premarket submission. The unreliable data raises concerns about the quality and integrity of associated premarket submissions, which may put public health and safety at risk.Your written response is inadequate. You acknowledge in your response that “there are issues with personnel's understanding of 21CFR Part 58 and the implementation of standard operating procedures,” including that “It was found during the inspection that QA was unfamiliar with GLP regulations” and that “[d]uring the investigation, it was shown that SD cannot clearly understand the responsibilities required in 21CFR part 58.” The response provided indicates that certain standard operating procedures (SOPs) relevant to the concerns noted in the Form 483 were revised, new procedures related to data integrity were developed, and some related staff training was conducted. Additionally, the response stated that new electronic systems for document management and training will be implemented and additional training provided. However, your response does not provide: (1) documentation of actions that have been or will be taken to fully address and correct the specific violations observed during the studies, including the conditions which allowed them to occur; (2) detail regarding how your testing facility will ensure that GLP regulations and applicable SOPs will be followed to ensure the quality and integrity of data generated in a study; (3) detail regarding how appropriate documentation/follow-up will be ensured when deviations arise in the future; (4) detail regarding planned preventive actions such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training of new study directors, as applicable; and (5) detail regarding how the effectiveness of proposed preventative actions such as the implementation of electronic systems (which have not yet been implemented) will be assessed. Thus, your response does not provide assurance that similar violations would not occur again. Your explanation, when taken into consideration with the violations described above, which occurred in multiple studies with various study directors over many months, suggests systemic failures in study director oversight of nonclinical laboratory studies and brings into question the quality and integrity of safety data collected at your testing facility.2. Failure to properly identify specimens used in nonclinical laboratory studies by test system, study, nature, and date of collection [21 CFR 58.130(c)].Not all specimens were identified by test system, study, nature, and date of collection. This information was not located on the specimen container or did not accompany the specimen in a manner that precluded error in the recording and storage of data. Your failures to adhere to this requirement include, but are not limited to, the following examples:a. Six muscle implantation studies ((b)(4)) conducted on a high-risk device had the following deficiencies regarding the histopathology slides that contained the study specimens:The slides did not have a study ID and were only identified by the numbers 1-20 written in pencil. There was also no information provided about the test system, nature, or the date of collection. Additionally, the animal identification numbers in the related source records for all six studies do not correspond to the labels on the slides. The animal and implant site identification in the source records only included numbers 1-10, and therefore, the slides are not attributable. In addition, the animal identification numbers in the source records were the same for both the tests and controls (both were labelled 1-10), such that test and control samples cannot be distinguished.Some of the numbers written on the slides were no longer legible and it appeared some numbers had been wiped off and/or written over, including the complete set of slides for study(b)(4)Week 4 and(b)(4)Week 13. These slides therefore have no identification at all.Failure to properly label specimens in a manner that precludes error in the recording and storage of data can attribute to evaluating specimens for the wrong animal, wrong implant site, and wrong study. Therefore, the reliability and quality of data of these studies are in question. This in turn adversely impacts a manufacturer’s and FDA’s ability to assess the overall safety and risk of the subject device prior to use in humans as a legally marketed device or for purposes of beginning clinical trials.Your written response is inadequate. You acknowledge that the procedure lacks some instructions for the study ID requirements and that correct identification was not included on the specimens. The new procedure has details regarding how to identify the slides, blocks, etc. However, your response does not address the issue of providing a unique animal identification system that would allow adequate traceability of specimens to prevent attribution of incorrect or invalid histopathology data to the test articles under study. Therefore, your written response does not provide assurance that similar violations would not reoccur.3. Failure to ensure that warm-blooded animals, excluding suckling rodents, receive appropriate identification [21 CFR Part 58.90(d)].Warm-blooded animals, excluding suckling rodents, used in laboratory procedures that require manipulations and observations over an extended period of time or in studies that require the animals to be removed from and returned to their home cages for any reason, shall receive appropriate identification. Your failures to adhere to this requirement include, but are not limited to, the following examples:a. Some source records do not include unique animal ID numbers. For example:In the AST study,(b)(4), both the test and control animals are only identified as numbers 1 through 5, which is not consistent with SOP(b)(4): Animal Marking Method.In muscle implantation studies, rabbits implanted with control and test articles are both named only “1”, “2”, or “3,” without identifiers to indicate the study numbers for these animals or to distinguish between control and test.Identifying multiple animals in a particular study with the same number, as noted above, indicates that the animals did not receive appropriate identification. Failure to properly identify each animal within an animal-housing unit raises concerns about the potential for animals to be incorrectly assigned to studies or study groups. The accuracy of study results cannot be verified since the ability to identify specific animals is foundational to being able to draw scientifically valid conclusions from the studies.Your written response is inadequate. You acknowledge the observation and have identified the root cause as being due to inadequate procedures and have acknowledged that the non-traceability of animal identification numbers can lead to the loss of tracking of testing systems, which can affect the reconstruction of experiments and data integrity. Proposed corrective actions include the revision of procedures, creation of new procedures and creation of guidelines for electronic data management. Your response indicates that your corrective and preventive action plan has been initiated to track animal numbers for testing for high-risk products. However, this does not appear to be adequate. This action should include all animals received and used at the facility to address the overall system and not isolated practices or only for certain products. Also, as not all of the corrective actions have been implemented at this time, the adequacy cannot be evaluated. Therefore, your written response does not provide assurance that misidentification of animals would not reoccur.4. Failure to conduct nonclinical laboratory studies in accordance with the protocols [21 CFR 58.130(a)].Nonclinical laboratory studies shall be conducted in accordance with the study protocol(s). Your failures to adhere to this requirement include, but are not limited to, the following examples:a. Regarding the ongoing GPMT studies ((b)(4)and(b)(4), both started on(b)(4)), on(b)(4)none of the guinea pigs' cages contained water bottles. Study protocols(b)(4)and(b)(4)Animal management, states “Water: Drinking water met the Standards for Drinking Water Quality(b)(4)5749-2022.” However, no water was observed to be provided to the guinea pigs, and when asked, the veterinarian stated they used cabbage as the water source. Additionally, it was observed that feed pellets were intermixed with bedding/excreta. Per the aforementioned protocol, feed should consist of “Full-price pellets,(b)(4).” and there should be “no known contaminants present in the feed, water, or bedding expected to interfere with the test data.” Additionally, in multiple cages, the feed box was empty and feed pellets fell into the beddings through the spacings between metal wires of the feed box. Due to the large gaps between the wires of the feed box, the feed box could not provide “reliable and easy” access for guinea pigs to eat the feed pellets. Per the SOP(b)(4)-SOP-IAC-001 Animal welfare, Section 3.2, “Drinking and feeding devices for animals should be safe, reliable and easy to eat, and should be kept clean and in normal use.”b. Within the aforementioned studies, on(b)(4), it was observed that the recorded weights for multiple guinea pigs were less than 300 grams (22 of 30 in the(b)(4)study and 24 of 30 in the(b)(4)study). Per study protocols(b)(4)and(b)(4), section 7.2 Test Animal, all animals should weigh 300-500 grams at the initiation of the study. Per the study protocols and internal procedure(b)(4)-SOP-BIO-003, all animals should weigh 300 - 500 grams at the initiation of the study.Failure to follow the protocol impacts the reliability and quality of data contained within the final study report. This in turn adversely impacts a manufacturer’s and FDA’s ability to assess the overall safety and risk of the subject device prior to use in humans as a legally marketed device or for purposes of beginning clinical trials. Deprivation of food and water is inhumane, and can have adverse effects on animal growth, the immune system, and metabolic state, as well as impact how the body responds to the extract (i.e., device) that is being tested, thus impacting the reliability of the data generated from the nonclinical laboratory studies conducted at your testing facility. Likewise, utilizing animals that do not meet the protocol-specified weight requirements can impact the interpretation and validity of the test results.Your written response is inadequate. You acknowledge the concern raised by the investigator that not all nonclinical laboratory studies were conducted in accordance with the protocol. Your response indicates that certain SOPs relevant to the concerns noted in the Form 483 were revised, protocol amendments and deviations for certain studies were documented, training for the laboratory supplier was conducted, and a plan was developed for inviting a third-party consultant to audit the animal tracking process. However, your response does not: (1) demonstrate how you will ensure that all personnel will follow study protocols; (2) provide documentation of deviation incidents for all impacted studies; and (3) address any planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance following completion of the submitted audit plan or future training for new staff and/or new procedures, as appropriate. Therefore, your written response does not provide assurance that similar violations would not occur again.5. Failure of the Quality Assurance Unit (QAU) to maintain a copy of a master schedule sheet of all nonclinical laboratory studies conducted at the testing facility indexed by test article and containing the test system, nature of study, date study was initiated, current status of each study, identity of the sponsor, and name of the study director [21 CFR 58.35(b)(1)].Your failures to adhere to this requirement include, but are not limited to, the following examples:a. Of the 26 studies requested, 14 of them listed below were not found on the master schedule (MS):(b)(4)b. The MS has not been updated since September 30, 2024. However, studies(b)(4)and(b)(4), which were not included in the MS, were observed to be ongoing on(b)(4).c. The MS does not include the name of the study director, the test system, or the sponsor.A reliable QAU is integral to the successful completion of any nonclinical laboratory study. Without appropriate QAU oversight, neither the sponsor nor FDA reviewers have assurance that the data in the final study report is accurate and valid. Failure to perform QAU functions can have a negative impact on a study because it indicates a lack of monitoring and oversight of each study to ensure compliance with all applicable GLP regulations, and calls into question the quality and integrity of studies conducted.Your written response is inadequate. You acknowledged in your response the concern that the quality assurance unit failed to maintain a copy of a MS sheet that contained all required elements for all nonclinical laboratory studies, and you indicated that this was likely due to an inadequate MS procedure, as well as QA personnel having overlooked their responsibilities. Your response indicates that SOP(b)(4)-SOP-GEN-008 Master Schedule will be revised, QA personnel will be trained on responsibilities, and the FDA GLP studies in the past three years will be sorted out and “a complete GLP master plan” will be submitted to FDA. However, your response does not address how missing studies will be systematically identified and included in the MS. In addition, your response does not discuss whether there will be preventative actions implemented such as audits to check for compliance to the SOPs, nor does it discuss future training for new staff and/or new implemented procedures as applicable. Therefore, your response does not provide assurances that QAU failures will be avoided in the future.6. Failure to prepare final reports that were signed and dated by each of the individual scientists or other professionals involved in the studies [21 CFR 58.185(a)(12)].Nonclinical laboratory study results are to be documented in a final study report that must include the signed and dated reports of each of the individual scientists or other professionals involved in the study. Your failures to adhere to this requirement include, but are not limited to, the following example:The final reports of all of the seven muscle implantation studies for significant risk devices that were reviewed ((b)(4)through(b)(4)) did not include the signature of the responsible pathologist that provided the histopathology assessment. The pathologist’s signature and date were also missing on the source records where the tissue reaction scores were reported.Inclusion of the dates and signatures ensures that the findings of the study results can be attributed to the individual scientist completing the study and helps to provide confirmation that the findings are accurately reflected. Without this documentation, it is unknown if the pathologist was involved in the generation of these reports, and whether the data truly reflect the pathologist’s findings. These failures raise questions about the quality and integrity of data collected at your facility.Your response is inadequate. Your response indicates that SOP(b)(4)-SOP-ORG-003 Study Director Duties and Responsibilities was revised, personnel training was conducted, and a plan was developed for inviting a third-party consultant to audit the pathological report management process. Additionally, you indicated that the final reports of high-risk products from 2020-2024 would be reopened to supplement pathological report and evaluate the impact. However, you have not detailed how you intend to assess and supplement these reports. Additionally, while you have revised the aforementioned SOP, the revisions made do not address the fact that a final report should include the signed and dated reports of each of the individual scientists or other professionals involved in the study. Your response also does not discuss whether there will be preventative actions implemented such as frequency (e.g., quarterly, annual) of audits to check for compliance following completion of the submitted audit plan or future training for new staff and/or new procedures, as appropriate. Therefore, your response does not provide assurances that these failures will not reoccur.7. Failure to provide for orderly storage and expedient retrieval of all raw data, documentation, protocols, specimens and interim and final reports [21 CFR 58.190(b)].GLP regulations require that archives are maintained in a way that allows for orderly storage and expedient retrieval of all raw data, documentation, protocols, specimens, and interim and final reports. Your failures to adhere to this requirement include, but are not limited to, the following examples:a. Your study archives are not organized to permit expedient retrieval. It was observed that records from multiple different studies were stored together in at least 30 boxes without any labels, and GLP study records could not be readily located. On(b)(4), it took up to eight employees over two hours to locate records from eight studies that should have been in the GLP archive room. Two sets of study data were found in the GLP archive room and the remaining six were in the non-GLP storage room.b. The original final study report for GPMT study(b)(4)was amended on 10/12/22; however, a copy of the original report was not retained in the GLP archive portable hard drive. It was stored in the non-GLP public folder.Inadequate archiving practices could result in the loss or destruction of study material, prevent, or reduce the ability to confirm or amend study results, and puts the archive data at risk of being attributed to the incorrect study. Further, having the raw data readily accessible to the FDA reviewer enables the study to be verified as needed to facilitate review and helps to ensure patient safety. Based on these failures, FDA has concerns about the quality and integrity of the data generated from the nonclinical laboratory studies conducted at your testing facility.Your response is inadequate. Your response indicates that SOP(b)(4)-SOP-ORG-005 Archival, Maintenance and Retrieval, Disposal and Transfer of Records and Materials has been revised, and that you intend to take additional actions, including expansion of the archiving area, adding personnel, and verifying and recovering the completed studies. However, your response does not provide complete documentation of actions that have been or will be taken to fully address and correct the specific violations observed during the inspection, including the conditions that allowed them to occur or detail regarding planned preventive actions such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training of new personnel, as applicable. Therefore, your response does not provide assurance that these failures have been corrected and will not reoccur.In addition to the violations described above, we have concerns about the records generated during GLP studies that were not maintained in a manner to prevent unauthorized access, changes, or deletions, which further calls into question the reliability and integrity of the data. The histopathology results were transferred between the current pathologist and study director on a portable USB device with a shared password and stored in an unlocked cabinet in the pathologist’s reading room. In addition, for 14 of the 24 studies inspected, the study director has her username and password(b)(4), which would allow anyone to log in.The study director’s workstation is an open cubicle within a large office that did not have controlled access. The combination of shared password access and unsecured physical storage increases the vulnerability of critical data to be altered or deleted by unauthorized individuals. The absence of physical security measures increases the likelihood of unauthorized individuals accessing not only the study director’s laptop but also any sensitive data saved in the laptop.The violations described above are not intended to be an all-inclusive list of problems that may exist with your facility. It is your responsibility as a non-clinical laboratory to ensure compliance with the Act and applicable regulations.Within 15 working days of receiving this letter, please provide documentation of the additional corrective and preventative actions that you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which you are the testing facility. Any submitted corrective action plan should include projected completion dates for each action to be accomplished as well as a plan for monitoring the effectiveness of your corrective actions. In addition, please provide a complete list of all nonclinical laboratory studies of FDA-regulated devices for the last five years, including the name of the study, the test article, the name of the study director and sponsor, and the current status of the study. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. In addition, FDA could initiate disqualification proceedings against you in accordance with 21 CFR 58.202. If you believe that you have complied with the FD&C Act and FDA regulations, please include your reasoning and any supporting information for our consideration.Your response should reference “CTS# EC250057/E001” and be sent via email to: Irfan.khan@fda.hhs.gov.A copy of this letter has been sent to FDA’s OBMI Foreign Inspection Cadre via email FDAInternationalBIMO@fda.hhs.gov. Please send a copy of your response to that office.If you have any questions, please contact Adaliz Santaliz-Cruz by phone at (787) 729-9024 or email at Adaliz.Santaliz-Cruz@fda.hhs.gov.Sincerely yours,/S/Soma Kalb, PhDDirectorDCEA1: Division of Clinical Policy and QualityOffice of Clinical Evidence & AnalysisOffice of Product Evaluation and QualityCenter for Devices and Radiological Health______________________1Facilities must have space provided for archives that is “limited to access by authorized personnel only, for the storage and retrieval of all raw data and specimens from completed studies.” 21 CFR 58.51; see also 21 CFR 58.190(d).

行政处罚案件信息摘要行政处罚决定书文号湘药监妆罚〔2025〕32号当事人湖南素玳生物科技有限公司组织机构代码91430100MA4L2XLY6K法定代表人石凤华违法类型湖南素玳生物科技有限公司经营不符合技术规范的化妆品案行政处罚内容1.没收违法所得27540.00元，没收120盒素玳胶原蛋白弹力紧致面膜违法产品。2.处货值金额28080.00元1倍罚款，罚没款共计55620.00元。作出行政处罚决定的行政机关湖南省药品监督管理局作出行政处罚决定的日期2025年8月18日备注

序 号行政处罚决定书文号违法企业名称或自然人姓名法定代表人姓名违法企业组织机构代码违法行为类型主要违法事实行政处罚的内容行政处罚的依据履行方式和期限作出处罚决定的行政机关和日期1鄂药监襄阳械处罚〔2025〕1号湖北好德快生物医药技术有限公司林俊光91420684MA7EMBA06B生产标签不符合规定的医疗器械当事人生产的医疗器械远红外治疗贴外包装正面标签明确标示有“膝盖止痛型”字样，与该公司取得的《医疗器械注册证》批准的产品型号表述不一致，且该产品说明书也没有“膝盖止痛型”表述和字样。违反了《医疗器械说明书和标签管理规定》第四条第二款、第三款的规定罚款依据《医疗器械说明书和标签管理规定》第十八条和《医疗器械监督管理条例》第八十八条第（二）项的规定主动履行，当事人收到行政处罚决定书之日起十五日内湖北省药品监督管理局2025年08月19日

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Mr. George LeMaitreChairman and CEOLeMaitre Vascular, Inc.63 Second Ave.Burlington,MA01803United Statesglemaitre@lemaitre.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 713502August 11, 2025Dear Mr. LeMaitre:During an inspection of your firm located in North Brunswick, NJ from March 4, 2025, through April 16, 2025, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures Artegraft Collagen Vascular Grafts. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.Quality System Regulation ViolationsThis inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,Code of Federal Regulations(CFR), Part 820. We received responses from Monte Nelson, Sr. Director, Quality Affairs - Artegraft dated May 7, 2025, and August 5, 2025, concerning our investigators’ observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address the May 7, 2025, response below, in relation to each of the noted violations. Any additional responses will be reviewed as part of your response to this letter.These violations include, but are not limited to, the following:1. Failure to establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(e). Specifically,a. USP water sampling procedures utilized by your firm for testing of conductivity, Total Organic Carbon (TOC), endotoxin, and microbial contamination contain inconsistent and conflicting requirements that ensure water being sampled is representative of water used in production of the Artegraft Collagen Vascular Graft devices. Specifically,i. Water samples for monitoring are being taken through a(b)(4)and not(b)(4)from the Point of Use (POU) as required by SOP 103, Sampling of the USP(b)(4)Water Systems, section 6.5 states that(b)(4)samples be tested from points of use (POU) according to FRM 103-03.ii. SOP 103 is not adequate since it requires the water to be purged after system sanitization for(b)(4)sampling (section 6.12.1), requires the system to be flushed for at least(b)(4)sampling (section 6.12.2), and requires the sample port to be sprayed with(b)(4)sampling (section 6.12.5). The purging, cleaning, and spraying the sample port with(b)(4)sampling are not representative of the(b)(4)use of the water system used during production.iii. WI MFG-040, Operation of the USP(b)(4)Water system Equipment ID #(b)(4)is not adequate since it states sample valves (SVs) will be cleaned when sampling is performed in accordance with SOP 103 (section 6.8.11.2) and states that(b)(4)POUs ((b)(4)-POU) only will be cleaned when(b)(4)is necessary, and(b)(4)system sanitation has been performed (section 6.8.11.3). This cleaning and sanitation(b)(4)sampling are not representative of the(b)(4)use of the water system used during production.b. Your firm changed the sterilant solution used for sanitization of the USP(b)(4)Water Systems utilized in the manufacturing process. Your firm utilizes procedure MP-059, Preventive Maintenance of the USP(b)(4)Water Systems which in sections 6.4.2 and 6.4.3 specify that(b)(4)Solution is used. However, the Maintenance Log Sheet for the USP Water System Monitoring (FRM MP-06; dated 11/27/24) states that(b)(4)was used for system sanitization. During the inspection, your firm’s Sr. Quality Engineer stated that(b)(4)was discontinued sometime in 2024. Your firm was unable to provide any documentation during the inspection that allowed for a different sterilant solution to be used per procedure MP-059, nor that your firm has assessed the impact of the new sterilant on devices manufactured by your firm such as on the biocompatibility or if the new sterilant has different ingredients (e.g., potential contaminants).c. Your firm is not documenting the(b)(4)replacement of(b)(4)during water sampling (section 6.5.2) which is required per SOP 103, Sampling of the USP(b)(4)Water Systems, which states that(b)(4)is to be replaced by a member of the quality team during(b)(4)water sampling as per SOP 102 – Workstation Cleaning Procedures for Within the LeMaitre Production Facility.d. The records for the Equipment ID #(b)(4)sanitizations performed on(b)(4)do not include written documentation that no residual sanitant remains in the system as required by MP 059, Preventive Maintenance for the USP(b)(4)Water System, which states in Section 6.4.5 (Section 5.5.5 of Exhibit F), that the(b)(4)utilized for system sterilization will provide written assurance that there is no sanitizer solution left in the system prior to releasing the system for use. WI-MFG-040, Operation of the USP(b)(4)Water system Equipment ID #(b)(4), and section 6.8.12.1 states the(b)(4)will provide written documentation stating that there is no residual sanitant in the system, post sanitation.We reviewed your firm’s response and conclude that it is not adequate. In your response, you provided data collected from an additional water sampling that is aligned with(b)(4)manufacturing that showed the water system conformed to USP(b)(4)Water specifications, revised SOP 103 to remove(b)(4)actions not reflective of(b)(4)use of the water system, WI MFR-40 to specify cleaning of the POU/SV/(b)(4)-POU should occur(b)(4)system sampling, and FRM 103-03 to allow for documentation of each required activity during water sampling. Your response also promises to revise SOP 001, PS 01, and FRM PS 01. Additionally, you provided updated MP-059 and FRM MP-006 documents that replaces(b)(4)with(b)(4)as well plans to update SOP 053 to require supplier change notifications to be sent to a new email address. However, your response did not provide an assessment of the new sanitant on the biocompatibility of the product or any other differences in ingredients (e.g., potential contaminants) and how your firm plans to monitor residual sanitant levels. Please provide this information and additional promised revised documents in your response to this letter.2. Failure to establish and maintain procedures to adequately control environmental conditions that could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c). Specifically, your environmental monitoring procedure, SOP 101, does not allow for environmental samples to be collected in a manner that is reflective of the production ((b)(4)) environment. For example:a. Section 6.5.2.3 of SOP 101 related to surface sampling states thateach designated workstation surface shall be cleaned per the(b)(4)method as described in SOP 102 prior to sample collection.b. Section 6.10.2 of SOP 101 related to swab sampling states thateach designated surface shall be cleaned per the(b)(4)method as described in SOP 102 prior to sample collection.c. Section 6.6.3 of SOP 101 related to viable air sampling states that the personnel traffic around the air sampler should be kept to a minimum so as not to artificially affect the data.d. Section 6.7 of SOP 101 related to non-viable air sampling does not specify when samples are to be taken ((b)(4)conditions).The adequacy of your firm’s response cannot be determined at this time. In your response you provided test results from preliminary sampling collected during normal production which exhibited nominal results and were within specification along with a revised SOP 101 that now requires sampling during(b)(4)production for all test locations and the removal of any requirement for cleaning(b)(4)sampling. Your response also promises to create a form to document all sampling during(b)(4)production, updates to SOP 001, and performance of(b)(4)sampling during(b)(4)production following the revised SOP 101. In your response, please provide an update on the status of these corrective actions.3. Failure to validate with a high degree of assurance and approve according to established procedures, a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR § 820.75(a). Specifically, your firm failed to adequately validate the(b)(4)sterilization process for the Artegraft Collagen Vascular Graft in accordance with recognized standards. According to your Sterilization Validation and Requalification document (WI-QA-012), your firm based the process sterilization validation on the requirements found in(b)(4)-(b)(4)-(b)(4)for validating the sterilization process used to sterilize your Artegraft devices. During review of the most recent 2023 performance qualification of the Artegraft Collagen Vascular Graft:(b)(4)sterilization process validation (VAL-PO2023) protocol and report it was noted that your firm failed to consider the bioburden of raw materials and/or components and their subsequent storage, and the control of the environment in which the product is manufactured, assembled, and packaged as required by(b)(4)and(b)(4),(b)(4)–Part 1: Application of Risk Management.The adequacy of your firm’s response cannot be determined at this time. In your response you conducted a risk assessment and began testing raw materials and components. Additionally, you plan to create a procedure for sampling, testing, and analyzing raw materials and sterile barrier bioburden, as well as performing an assessment to inform testing of future raw materials and components based on results and risk. In your response, please provide an update on the status of these corrective actions.4. Failure to establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b). Specifically, your firm has not provided a documented rationale establishing the following:a. Section 6.1 of SOP 100, Routine Product Bioburden Testing, states that(b)(4)Product Bioburden testing will be performed on a calendar(b)(4)bases, at a minimum. Your firm lacks documentation for how a(b)(4)frequency for bioburden testing was determined to be adequate to monitor and control the Artegraft grafts. In response to the previous FDA inspection, your firm initiated CAPA 00065. As part of this CAPA, you wrote a memo justifying the(b)(4)bioburden sampling frequency stating that thecurrent frequency follows the guidance in Annex A, Section A8.1of BS EN ISO 11737-1 :2018. However, six non-conformances for out of specification product bioburden samples were collected between September 2024 and March 2025 from the following lot numbers:(b)(4). There is no documented evaluation to determine if the testing frequency should be updated when out of specification bioburden test results are received. Your firm took no action based on these out of specification results justifying that decision as the organisms identified in the test were not as challenging as the sterilization challenge organism and repeat testing on a different lot of product did not result in out of specification product bioburden. Additionally, it is unclear if the sterilization process is capable of(b)(4)sterilization for bioburden levels as high as the challenge organism used during validation.b. Section 3.2 of SOP 100 defines Bioburden as:The quantity of viable microorganisms on or in product and/or sterile barrier system. However, your firm does not perform(b)(4)bioburden sampling of raw material and/or the sterile barrier components to assess their bioburden. The only documented testing of the sterile barrier was performed during the(b)(4)assessment of the(b)(4)primary packaging, performed in August 2006. Additional testing of the primary packaging has not been conducted.The adequacy of your firm’s response cannot be determined at this time. In your response you provided an updated justification of bioburden testing frequency, updates made to SOP 100 that clarify the scope of pre-sterile arteries(b)(4), plans to create a procedure for sampling, testing, and analyzing raw materials and sterile barrier bioburden, as well as performing an assessment to inform testing of future raw materials and components based on results and risk. In your response, please provide an update on the status of these corrective actions. Additionally, please clarify whether there were any updates considered for Section 6.10.3 of SOP 100 to include the need for increased bioburden monitoring frequency if any action level is exceeded.5. Failure to verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 820.100(a)(4). Your firm utilizes SOP 053, Supplier Management, for supplier monitoring and issuance of supplier corrective action reports (SCARs) if necessary. Section 6.6.6 of SOP 053 statesIf Corrective and/or preventive actions are deemed necessary CAPA may be initiated per SOP 050. Section 6.5.6 of SOP 050 lists the requirements to perform CAPA effectiveness verification. In review of the following three closed/completed supplier corrective action reports (SCARs) verification of effectiveness was not documented.a. 2023-02 – issued on May 26, 2023, for an identified trend of failing sterility test results from a testing(b)(4)b. 2023-03 – issued on June 20, 2023, for concerns of growth on sterility samples, including growth on the negative control, from a testing(b)(4).c. 2023-004 – Concerns nonconformances/observations identified during a(b)(4)audit for a sterility and bioburden testing(b)(4)We reviewed your firm’s response and conclude that it is not adequate. In your response you provided updated versions of SOP 053 (which now includes all criteria related to corrective actions; including but not limited to verification of effectiveness. Your response did not include effectiveness verification for previously closed/completed SCARs. Additionally, regarding SCAR 2023-02, please clarify the final disposition of grafts from lots(b)(4),(b)(4), and(b)(4)and provide additional justification for repeating the sterility test given that the(b)(4)investigation concluded (documented in a memo dated August 10, 2023) that “(b)(4).” Per USP Sterility Tests, a sterility test can be determined to be invalid only if it can be clearly demonstrated that the test was invalid for causes unrelated to the product to be examined. In your response, please provide the above information.6. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Specifically, your Corrective and Preventive Action (CAPA) procedure (SOP 050) is not being implemented in that section 6.5.3.1 of SOP 050 lists deadlines according to the identified risk of each CAPA according to Table 2 of SOP 050. There are three risk levels each with a deadline from starting an investigation to implementing a corrective or preventive action: High Risk –(b)(4); Medium Risk –(b)(4); Low Risk –(b)(4). The following are examples of CAPAs that did not meet your firm’s timeframes:a. High Risk CAPAi. CAPA-00068, concerns inadvertent release of nonconforming product. A total of 81 days elapsed from investigation to implementation.b. Medium Risk CAPAsi. CAPA-00075, environmental monitoring(b)(4)swab samples that were out of specification. A total of 216 days elapsed from investigation to implementation.ii. CAPA-00078, concerns out of specification bioburden results. A total of 120 days elapsed from investigation to implementation.c. Low Risk CAPAsi. CAPA-00072, concerns a trend of nonconformances related to differential pressure. A total of 121 days from investigation to implementation.The adequacy of your firm’s response cannot be determined at this time. In your response you provided an updated version of SOP 050 to include time for formal review and revisions if necessary and promise to review current open CAPAs and write formal extension plans, if necessary. In your response, please provide any extension plans created and an example of a CAPA that required additional investigation/planning time, including the justification for the additional time.Corrections and Removals ViolationOur inspection also revealed that your firm’s Artegraft Collagen Vascular Graft devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 806 – Medical Devices; Reports of Corrections and Removals. Significant violations include, but are not limited to, the following:Failure to submit any report required within 10 working days of initiating a correction or removal, as required by 21 CFR 806.10For example, your firm distributed(b)(4)grafts from lot 23DD203 manufactured using raw material Bovine Carotid Arteries control number(b)(4)from a non‐approved supplier, one of which was implanted in a patient. You recalled the devices sometime after 6/23/2023. Since the product was released prior to completion of the(b)(4)evaluation, as required by your firm’s procedure, and without notifying the FDA of the change in the supplier of critical materials for a Class III device, this lot of material is violative. Graft devices manufactured using raw material from an unapproved supplier could have compromised sterility or mechanical integrity, which may present a risk to health such as infection, aneurysm, pseudoaneurysm, rupture, or mechanical failure at the anastomosis leading to bleeding or explantation of the failed device. Therefore, your firm’s removal of grafts in lot 23DD203 meets the definition of a medical device removal initiated to remedy a violation which may present a risk to health, for which you are required to submit a Report of Correction or Removal to FDA. As of 7/1/2025, you did not submit a Medical Device Report of Correction or Removal to FDA for this action.Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.Your firm’s response should be sent via email to Establishment Assessment Team Assistant Director Gina Brackett at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 713502” when replying. If you have any questions about the contents of this letter, please contact: Sean Moynihan at sean.moynihan@fda.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.Sincerely,/S/Matthew G. HillebrennerDeputy DirectorOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCc: Ms. Cathleen I. VanDerVeer, Senior Vice President Operations, cvanderveer@lemaitre.comMr. Monte Nelson, Director of Quality Affairs, mnelson@lemaitre.com